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Among the 2.75 billion commercial airline passengers yearly, nearly 1 in 11,000 experiences an in-flight medical emergency, occurring in approximately 1 out of every 604 flights. Of these cases, 25% require hospital transport for further care upon landing.[1] The environmental conditions and activities involved in flight operations can exacerbate underlying pathology in otherwise stable physiology and psychology.[2] The most common in-flight illnesses include gastrointestinal events, respiratory and neurological concerns, and presyncope/syncope.[3][4] (Source: Centers for Disease Control and Prevention, 2024) Flight physicians specialize in identifying, preventing, and managing the physiological impact of flight-related stressors. Risk factors include advanced age, anxiety, altered circadian rhythms, drug or alcohol intake, and flight-associated environmental stressors. These stressors may involve exposure to low oxygen levels, hypobaric and hyperbaric changes, microgravity and macrogravity, vibration, or impact.[5] Most healthy individuals tolerate these conditions without difficulty, but they can acutely worsen stable chronic diseases. Additionally, passengers may experience acute medical events unrelated to flight while aboard an aircraft.[6] When a passenger experiences a medical emergency in flight, the crew requests assistance from any healthcare professionals on board. Medically trained individuals should identify themselves and provide aid. Qualified medical responders who provide their expertise are legally protected under the 1998 Aviation Medical Assistance Act (AMAA). The most experienced responder should take charge, coordinating with the flight crew trained in cardiopulmonary resuscitation (CPR) and initiating stabilization measures using the onboard first aid kit, emergency medical bag, and, if available, an automated external defibrillator (AED). If additional expertise is required, ground-based physicians may be consulted via radio. These interventions also help the crew determine whether diversion to an alternate airfield is necessary, a decision historically made in approximately 1 out of every 9,000 flights.[7]